Bone grafts are used in roughly two million orthopedic procedures each year, and generally take one of three forms. Autografts, which typically consist of bone harvested from one site in a patient to be grafted to another site in the same patient, are the benchmark for bone grafting materials, inasmuch as these materials are simultaneously osteoconductive (serving as a scaffold for new bone growth), osteoinductive (promoting the development of osteoblasts) and osteogenic (containing osteoblasts which form new bone). However, limitations on the supply of autografts have necessitated the use of cadaver-derived allografts. While they are more available that autografts, allografts may trigger host-graft immune responses or may transmit infectious or prion diseases, and are often sterilized or treated to remove cells, eliminating their osteogenicity.
The shortcomings of human-derived bone graft materials have fed a growing interest in synthetic bone graft materials, which typically comprise calcium ceramics and/or cements delivered as pastes or putties. These materials are osteoconductive, but not osteoinductive or osteogenic. To improve their efficacy, synthetic calcium-containing materials have been loaded with osteoinductive materials, particularly bone morphogenetic proteins (BMPs), such as BMP-2, BMP-7, or other growth factors such as fibroblast growth factor (FGF), insulin-like growth factor (IGF), platelet-derived growth factor (PDGF), and/or transforming growth factor beta (TGF-ß). However, significant technical challenges have prevented the efficient incorporation of osteoinductive materials into synthetic bone graft substitutes which, in turn, has limited the development of high-quality osteoinductive synthetic bone graft materials.
One challenge has been the development of a graft matrix which delivers an osteoinductive material over time, rather than in a single short burst release, and which has appropriate physical characteristics to support new bone growth. The production of a material with appropriate physical characteristics involves balancing several competing needs: the ideal materials should be rigid enough to bear loads applied to the graft during and after implantation; they should have sufficient porosity to allow for cell and tissue infiltration; they should degrade or dissolve at a rate which permits its replacement by new bone; and they should elute osteoinductive material in a temporal and spatial manner that is appropriate for bone generation. An optimal graft matrix, which meets each of these design criteria, has not yet been realized, and BMP-eluting synthetic bone grafts currently available commercially do not meet these requirements. Accordingly, need exists for a synthetic bone graft material which reconciles these competing needs and which provides optimal release of osteoinductive materials, particularly BMPs.